Increasing interest has been focused on lncRNAs as potential markers in the pathogenesis and progression of numerous diseases.

We aimed to investigate the expression pattern and role of cell-free lncRNAs (GAS5, HCG27_201 and LY86-AS1) in pre-diabetic, diabetic and T2DM groups.

Quantification of the expression level of cell-free lncRNAs (GAS5, HCG27_201 and LY86-AS1) was performed by real-time PCR in 210 individuals classified in diabetic (T2DM), pre-diabetic and control groups.

Significant differences were observed in the relative expression level of lncRNAs (GAS5, LY86-AS1 and HCG27_201) among the three studied groups. The LncRNA expression levels decreased gradually from the control to the pre-diabetic group and reached the lowest values in the T2DM group. The A receiver operating characteristic curve (ROC) was applied to identify a cut-off value for each of the three genes among our groups. The three lncRNAs showed promising results in discriminating between the diabetic patients and controls, with HCG27_201 gene expression having the best performance. Furthermore, lncRNA expression was able to predict the future development of DM in the pre-diabetics because ROC analysis among diabetics and pre-diabetics revealed considerable results. GAS5 gene expression showed the best performance. Additionally, HCG27_201 expression was the most valuable biomarker for differentiating between pre-diabetics and controls and presented a sensitivity of 91% and specificity of 64%.

We concluded that cell free lncRNAs (GAS5, LY86-AS1 and HCG27_201) could be considered promising diagnostic and predictive biomarkers for DM and that HCG27_201 could act as a potential diagnostic biomarker for pre-diabetes.